Focus on Concussion Detection Turns to Blood Biomarkers

The CDC recently submitted a report to Congress that addresses critical gaps in knowledge in the diagnosis, treatment, and prevention of traumatic brain injuries, but ongoing research could quickly deem the report out of date.

The report, meant to document the number of people in the U.S. affected by traumatic brain injury (TBI) and the effectiveness of TBI rehabilitation, spins the diagnosis forward by demonstrating TBI’s impact on society and the economy.

Among the many gaps addressed in the report, the CDC recommended that improvements be made to several major categories, including: data collection on TBI incidence and prevalence, especially for cases of TBI treated in non-hospital settings and those that are not receiving medical care; measurement of rehabilitation success in various patient populations; and rehabilitation research, including more studies on effectiveness of timing, intensity, and frequency of rehabilitative therapy.

Research in Action

Meanwhile, researchers from Brown University and Lifespan health system are making headway in a least one of those categories. The research team identified a panel of four readily detectable blood proteins that can accurately indicate concussion, according to study results published in the Journal of Neurotrauma.

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The search for blood biomarkers for concussion is not new, however the researchers’ strategy for using biomarkers that can be easily detected by widely available lab arrays — as opposed to exotic or proprietary antibodies — makes the discovery especially notable.

The four proteins, copeptin, galectin 3, matrix metalloproteinase 9, and occludin, change dramatically in the bloodstream after a concussion. Further, the correlation of proteins galectin 3 and occludin uniquely distinguish patients who suffer concussion from those who suffer an orthopedic injury like a bone break.

For the study, the researchers recruited an experimental group of 55 emergency room patients with concussions diagnosed by other means, a control group of 44 uninjured people, and a control group of 17 patients with long-bone fractures. All of the patients were measured for 18 proinflammatory proteins.

Within eight hours of injury, the concentrations of galectin 3, matrix metalloproteinase 9, and occludin were four-times greater, and the concentration of copeptin was three-times less in concussed patients compared to the uninjured controls. Elevated levels of these proteins were also observed in some controls, however none had high levels of two or more proteins, compared to 90% of concussed patients who had significant level alterations in two or more proteins.

High levels of copeptin, galectin 3, and matrix metalloproteinase 9 in concussed patients resulted in a high degree of sensitivity and specificity for injury compared to controls. In additions, researchers found that only in concussed patients did levels of occludin correlate with levels of galectin 3, differentiating the concussed patients from those with orthopedic injuries, who also had high levels of copeptin, galectin 3, and matrix metalloproteinase 9.

“This was a broad spectrum of the population with different genders, different ethnicities, different age, and different physical conditions, and on this background these four biomarkers were not influenced,” said researcher Joanna Szmydynger-Chodobska, MD.

The team of researchers has now turned their attention to developing a microfluidic chip that can produce reliable blood readings within two hours, making the test even more accessible and useful in emergency settings.

However, the panel of biomarkers may have use beyond the emergency room. The research team may continue to explore the potential of the protein biomarkers as therapeutic targets, pointing to the relationship between inflammatory proteins and the blood-brain barrier.